Project Summary This proposal focuses on uncovering new radical-based catalytic methodologies that facilitate the synthesis of bioactive compounds. Organic radicals are highly reactive species with unique chemoselectivities that complement canonical two-electron chemistry. Recently, the emergence of new catalytic strategies that leverage single-electron redox events and harness radical intermediates for the selective functionalization of organic molecules has provided chemists with useful tools for solving contemporary synthetic problems. However, the highly reactive nature of many organic radicals has made it difficult to impart catalyst-control over the selectivity of these fleeting intermediates, especially when complex reaction systems are concerned. In particular, catalytic stereoselective reactions involving free radical intermediates remain limited, and the discovery of such processes is highly desirable. To provide new radical-based platforms for reaction discovery and synthetic innovation, we recently developed a novel catalytic approach that exploits the unique redox features of Ti complexes. Specifically, we advanced a new strategy?radical redox-relay catalysis?for the development of redox- neutral reactions that combines single-electron oxidation and reduction events in the same catalytic cycle. This strategy was successfully implemented in the stereoselective Ti-catalyzed cycloaddition of N-acylaziridines or cyclopropyl ketones with alkenes as well as Ti/Co co-catalyzed rearrangement of epoxides to allylic alcohols. On the strength of these promising results, we anticipate that such radical catalysis strategies will ultimately emerge as powerful tools for solving a wide range of long-standing synthetic problems. Each project in this proposal applies our general strategy of Ti redox catalysis to address a prominent challenge in organic synthesis. Specifically, we aim to develop reactions that achieve enantioselective [3+2] cycloaddition, enantioselective epoxide isomerization, synthesis of skipped enones, and isomerization of aziridines to allylic amines. These transformations are either currently unknown or have significant limitations in reaction scope, efficiency, or selectivity. We will also carry out in-depth studies using canonical physical organic and electrochemical techniques to gain insights into the mechanisms of these reactions. The development and mechanistic understanding of these proposed transformations will represent significant advances for the field of organic synthesis.